Exposure to toxic heavy metals continues to be a major occupational and environmental problem around the world. Exposure occurs through environmental sources of contaminated food, water and air. The most common acute and/or chronic heavy metal toxicities are related to lead, arsenic, and mercury. These environmental heavy metals bind to hydroxyl, amino, and sulfhydryl containing groups in proteins, resulting in alterations of enzymatic activity. The affinity of metal species for sulfhydryl groups serves a protective role in heavy metal homeostasis as well. Increased synthesis of metal binding proteins in response to elevated levels of a number of metals is the body's primary defense against such poisoning.
Lead is the most significant heavy metal toxin and is related to exposure because lead has been added to paints, dyes, and gasoline. The inorganic forms of lead are absorbed through ingestion or inhalation and organic lead salts are absorbed through the skin. In adults, about 10% of an ingested dose is absorbed while children may absorb as much as 50%. Lead toxicity affects the central nervous and peripheral nervous systems and the blood, renal, gastrointestinal, cardiovascular, and reproductive systems. Lead can be found in erythrocytes (10%) and in bone (80 to 90%). Soft tissue in kidney and brain also store lead. Lead passes the placental barrier and is found in breast milk.
Chronic lead exposure is the most common toxicity in the United States. Lead poisoning from lead ingestion affects more than 2 million preschool-aged children. If left untreated heavy metal toxicities can result in significant morbidity and mortality. Encephalopathy is a leading cause of mortality in patients with both acute and chronic heavy metal toxicity.
Mercury and arsenic are also environmental poisons that can cause acute, sub-acute and chronic toxicity. Chronic toxicity is marked by neurological effects ranging from lethargy to excitement to tremor. Ligand formation is the basis for much of the transport of heavy metals throughout the body. However, some metals, like lead, compete with ionized species such as calcium and zinc to move through membrane channels in the free ionic form and follow calcium pathways to deposition in bone. Chronic exposure to mercury compounds may also lead to renal and hepatic failure and deterioration of alveolar bone with loosening of the teeth.
Exposure to arsenic is a major health concern in developing countries. The contamination of ground water is a frequent source of the arsenic and is highly prevalent in areas of gold mining. Gold miners have a high incidence of chronic arsenic poisoning.
Nearly all organ systems are involved in heavy metal toxicity. The most common include the central and peripheral nervous systems and the gastrointestinal, hematopoietic, renal, and cardiovascular systems. Lead toxicity also involves the musculoskeletal and reproductive systems. The organ systems affected and the severity of the toxicity vary with the particular heavy metal involved, the age of the individual, and the level of toxicity.
Today, toxicity due to chronic exposure to heavy metals is much more common than acute poisonings.
Even low-level environmental exposure to lead leads to a variety of chronic degenerative conditions. These conditions included cognitive disorders, hyperactivity, hypertension, renal insufficiency, cataract, cancer, and increased bone resorption. Thus, continuous exposure to low-levels of heavy metals is important to address.
Lead is a persistent metal and is still present in water, brass plumbing fixtures, soil, dust and important products manufactured with lead. Lead-based paint covers five billion square feet of nonresidential surface are in the US and almost 90 percent of the nation's bridges. Data now implicate low-level exposure and blood lead levels previously considered normal as causative factors in cognitive dysfunction, neurobehavioral disorders, neurological damage, hypertension and renal impairment. Issues surround the assessment of body lead burden and the consequences of low-level environmental exposure are critical in the treatment of chronic disease related to lead toxicity.
Another problem is the effects of these heavy metals on antioxidants. Cadmium and arsenic initiate the production of free radicals to cause tissue inflammation and genetic damage. Maintaining adequate levels of antioxidants will likely play an important role in treating heavy metal pathologies.
Nearly all fish and shellfish contain traces of mercury. The risks from mercury in fish and shellfish depend on the amount of fish and shellfish eaten and the levels of mercury in the fish and shellfish. For most people, the risk from mercury by eating fish and shellfish is not a health concern. Yet, some fish and shellfish contain higher levels of mercury that may harm an unborn baby or young child's developing nervous system. The Food and Drug Administration and the Environmental Protection Agency are advising women who may become pregnant, pregnant women, nursing mothers, and young children to avoid some types of fish and eat fish and shellfish that are lower in mercury.
Drinking water remains a major source of heavy metal exposure and is responsible for about 20 percent of the total daily exposure by the majority of the US population.
Ultrafiltration and reverse osmosis treatments produce high-quality water, but they are slow and the associated equipment and supplies are expensive. Another approach to this problem has been to use high surface area nanomaterials that actively absorb contaminants but do not restrict flow like membranes. Boehmite nanofibers that are 2 nanometers wide and 100 nanometer exhibit surface areas as high as 600 m2/g. Filters fabricated from these fibers remove bacteria, viruses and endotoxins from water by irreversibly binding the pathogens or toxins. These filters also non-selectively remove a variety of metal ions and ion mixtures from water. (US2008/084434)
Some of the compositions of the invention for lead removal are designed for oral use and may deliver chelating agents through the digestive tract and also need to be excreted. Because these compositions can also be used to deliver beneficial compounds when administered orally, another aspect of the invention is delivery of such compounds using specifically designed oral compositions similar to those designed for heavy metal removal and therapy.
The two principal routes of absorption across small intestinal epithelium are paracellular and transcellular. Lipophilic drugs are absorbed by the transcellular route, whereas hydrophilic drugs are slowly absorbed via the transcellular pathway or in some cases via the paracellular route.
Bioavailability of hydrophilic compounds is poor after oral administration, due to poor absorption of hydrophilic molecules and macromolecules across the mucosal surfaces of the stomach, intestine and colon. In addition, catabolic peptidase enzymes in the gastrointestinal tract can destroy peptide and protein drugs before being absorbed. Various delivery systems have been tried to improve oral absorption of drugs including, capsules, coated tablets, liposomes, biodegradable polymers, microemulsions of surface active agents, and biodegradable hydrogels. Drug absorption has been enhanced when additives are supplied to increase solubility, such as bile salts, anionic detergents, nonionic detergents, salicylates, acyl amino acids, and acylcarnitine. Other additives, such as zonula occludens toxin (zot), have been reported to influence the nature of tight junctions between enterocytes to increase intestinal permeability of hydrophilic compounds. Classifying drugs based on their water solubility and intestinal permeability has been used to predict bioavailability of a drug after oral ingestion. In one example, to create particles capable of adhering to the walls of the small intestine, albumin and albumin combined with 1,3-diaminopropane (DAP) are used. The invention compositions solve the problems set forth above.